Emicizumab as bleeding prophylaxis in children with von Willebrand Disease type 3 – a case series

Introduction: Van Willebrand Disease (vWD) Type 3 is the rarest and most severe form of vWD. Bleeding tendency includes mucocutaneous bleeding, but also joint bleeding and muscle bleeding, rarely intracranial hemorrhage. To date, therapy mainly consisted of von Willebrand Factor/Factor VIII (vWF/FVIII) concentrate supplementation on demand. If prophylaxis is considered, the factor concentrate has to be administered intravenously several times a week due to its short half-life. Emicizumab is a bispecific humanized monoclonal antibody, which bridges activated FIX and FX and thus takes over the function of FVIII. It is approved for prophylactic treatment in haemophilia A in all age groups, demonstrated to be safe and well tolerated. Emicizumab is administered subcutaneously every 1, 2 or 4 weeks. In severe vWD, emicizumab showed an improvement in thrombin generation ex vivo and in vivo. Several clinical case reports exist on adult and pediatric patients with vWD type 3 treated with emicizumab. However, emicizumab for vWD type 3 remains off-label use [1] [2] [3] [4] [5] [6] [7] [8] [9] [10].

Method: We present a case series of three children, reported according to the Case Report Guidelines (CARE).

Results: Case 1: 2.5-year-old boy, diagnosed with vWD type 3 at age 17 months with prolonged oral bleeding. Initially he was treated with FVIII/vWF concentrate on demand. To prevent repeated severe bleeds or joint bleeds, emicizumab was started off-label. Emicizumab was preferred over factor prophylaxis due to difficult venous access. To date, despite multiple mucocutaneus injuries, he experienced no relevant bleeding events while on emicizumab prophylaxis ([Fig. 1]).

Fig. 1  Bleeding severity of 3 patients with vWD Type 3 on emicizumab prophylaxis

Case 2: 12 year old boy, diagnosed with vWD type 3 at age 11 months. Experienced severe mucocutaneous, muscle and joint bleeds, and was treated with vWF/FVIII concentrates on demand, then switched to prophylaxis twice a week, which failed. At age 10.5 years prophylaxis with emicizumab was established. Improvement of severity of bleeding, but mucosal bleeds continue ([Fig. 1]).

Case 3: 9 year old girl, diagnosed with vWD type 3 at birth (positive family history). Experienced severe mucocutaneous, muscle and joint bleeds and was treated with vWF/FVIII concentrates on demand. At age 8 years, prophylaxis with emicizumab was started. Improvement of bleeding episodes but mucosal bleeds with need of vWF/FVIII concentrate remain ([Fig. 1]).

Conclusion: In patients with vWD type 3 and significant bleeding, the off-label use of emicizumab as bleeding prophylaxis can be an option to decrease severity of bleeding events and allows participating in school and sport activities.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

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